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Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis

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Abstract

Purpose

Benign and precancerous endometrial hyperplasias (EH) are differentiated thorough two possible histomorphologic classifications: WHO (adopting the subjective evaluation of cytologic atypia) and EIN (adopting several histomorphologic parameters, evaluable subjectively, or objectively with a computerized analysis calculating a prognostic score, the D score). ACOG recommends the use of EIN system although no distinction was made between objective assessment (not widely available), and subjective assessment (more applicable in the common practice). Moreover, it is still unclear if subjective EIN system is actually preferable to WHO classification. We aimed to assess the reliability of WHO system, D score and subjective EIN system in stratifying the risk of progression to cancer in EH.

Methods

MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, Cochrane Library and Google Scholar were searched for relevant articles from the inception to August 2018. All studies assessing the rates of progression of EH to cancer were included.

Results

Twelve cohort studies and one case–control study, assessing 3629 EH, were included. Relative risk (RR) for cancer progression was calculated with 95% confidence interval (CI), and results were compared using Chi-square test (significant p value < 0.05). WHO system showed a RR of 8.74 (95% CI 6.66–11.47). Objective D score showed a RR of 29.22 (95% CI 13.24–64.51), significantly higher than WHO (p = 0.005). Subjective EIN system showed a RR of 19.37 (95% CI 5.86–64.01), intermediate between WHO and D score, without significant differences (p = 0.20 and p = 0.57, respectively).

Conclusion

Objective EIN criteria with D score are significantly more reliable than WHO criteria in stratifying the risk of progression of EH to cancer. Subjective EIN criteria did not show significant superiority over WHO instead. Further studies are necessary to determine if subjective EIN system should replace WHO system in the routine diagnosis of EH.

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Authors and Affiliations

  1. Obstetrics and Gynecology Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy

    Antonio Raffone, Gabriele Saccone, Antonio Mollo, Giuseppe De Placido & Fulvio Zullo

  2. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, Naples, 80131, Italy

    Antonio Travaglino & Luigi Insabato

Authors
  1. Antonio Raffone
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  2. Antonio Travaglino
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  3. Gabriele Saccone
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  4. Luigi Insabato
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  5. Antonio Mollo
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  6. Giuseppe De Placido
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  7. Fulvio Zullo
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Contributions

AR, AT: protocol/project development, data collection, data analysis, and manuscript writing/editing. GS: data analysis and manuscript writing/editing. AM: protocol/project development and study supervision. LI: manuscript writing/editing and study supervision. FZ: protocol/project development, manuscript writing/editing and study supervision. GDP: protocol/project development and study supervision.

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Correspondence to Antonio Travaglino.

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Raffone, A., Travaglino, A., Saccone, G. et al. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet 299, 1233–1242 (2019). https://doi.org/10.1007/s00404-019-05103-1

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